Methods of improving tolerance related to feeding in an infant, toddler, or child

ABSTRACT

Disclosed are nutritional formulations including predigested fats that can be administered to preterm infants, infants, toddlers, and children for improving tolerance, digestion, and absorption of nutrients and for reducing the incidence of necrotizing enterocolitis, colic, and short bowel syndrome. The predigested fats include fatty acid-containing monoglycerides and/or a fatty acid component.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 13/333,936, filed Dec. 21, 2011, which claimspriority to, and any the benefit of, U.S. Provisional Application No.61/428,168 filed Dec. 29, 2010; U.S. Provisional Application No.61/428,173 filed Dec. 29, 2010; U.S. Provisional Application No.61/428,176 filed Dec. 29, 2010; U.S. Provisional Application No.61/428,177 filed Dec. 29, 2010; and U.S. Provisional Application No.61/428,185 filed Dec. 29, 2010, which disclosures are incorporated byreference in their entirety.

FIELD OF THE DISCLOSURE

The present disclosure relates to nutritional products comprisingpredigested fat and to methods for using the nutritional products. Moreparticularly, the present disclosure relates to infant, toddler, andpediatric products comprising fatty acid-containing monoglyceridesand/or a fatty acid component that provide nutritional benefitsincluding improved digestion, tolerance, and absorption of nutrients aswell as the reduction in the incidence of necrotizing enterocolitis,colic, and short bowel syndrome.

BACKGROUND OF THE DISCLOSURE

Nutritional liquids and powders, including infant and pediatricformulas, comprising a targeted selection of nutrients are well knownand widely available, some of which may provide a sole source ofnutrition, while others may provide a supplemental source. Thesenutritionals include powders that can be reconstituted with water orother aqueous liquids, as well as concentrated and ready-to-drinknutritional liquids such as milk or protein based emulsions. Thesenutritional liquids are especially useful when formulated with selectednutritional ingredients.

Although breast milk is generally recognized as the best nutrition fornewborn infants, not every mother can successfully breastfeed. Breastmilk replacers (infant formulas) may provide complete nutrition, andthey have been proven to meet infant normal growth and developmentalnutritional needs. Unfortunately, a small percentage of infant formulafed newborns can experience gastrointestinal (GI) intolerance problems,including loose stools, gas, necrotizing enterocolitis, colic, and thelike.

The GI intolerance problem may be at least in part due to incompletenutrient digestion and absorption in the infant. To address thistolerance problem, some infant formulas exclude lactose as aningredient, while others replace intact milk protein with hydrolyzedprotein to lessen the burden on an infant's digestion system.

Additionally, some formula fed newborn infants have a much lower fatabsorption rate than the breast fed infants. This discrepancy in fatabsorption rate decreases as infants become more mature. Presumably,newborn infants are deficient in lipase, and thus, they do not digestand absorb fat as well as breast fed infants who receive lipase in themother's milk.

A preterm infant's digestion system is less developed than that of aterm infant, yet they need more nutrients (calories) than term infantsto foster growth and development. Medium chain triglycerides (MCT oil)are easy to digest and absorb, and have been included in pretermformulas to improve formula fat, protein and calcium absorption. Themedium chain fatty acids included in the medium chain triglycerides,however, are not used to re-synthesize triglycerides to formchylomicrons after the MCT oil is digested and absorbed. As many lipidsoluble nutrients, such as carotenoids and vitamins A, D, E, and K, arebelieved to be packaged into chylomicrons prior to entering systemiccirculation, the benefit provided by MCT oil on lipid soluble nutrientabsorption, which is also important for growth and development, may bemore limited.

Although attempts have been made in the past to address the GI issuesand others set forth above, it would be desirable to provide infant andpediatric formulas that can provide nutritional benefits similar tobreast milk, and also provide good tolerance, digestion and absorptionof water-insoluble hydrophobic nutrients as well as a reduction in theincidence of conditions such as necrotizing enterocolitis, colic, andshort bowel syndrome. Additionally, it would be beneficial if theseformulas could be stabilizer free, and specifically carrageenan free.

SUMMARY OF THE DISCLOSURE

The present disclosure is directed to nutritional products, andspecifically to infant formulas, including predigested fat that includesfatty acid-containing monoglycerides and/or a fatty acid component.These nutritional compositions can advantageously be used for providingimproved tolerance, digestion and absorption of nutrients, includingwater-insoluble/lipid soluble nutrients, and for reducing the incidenceof necrotizing enterocolitis, colic, and short bowel syndrome. In someembodiments, the fatty acid component may be in fatty acid form orprovided as the calcium or magnesium salts of the fatty acid, thusproviding the additional benefit of additional nutrients.

One embodiment is a method of reducing the incidence of necrotizingenterocolitis in an infant, toddler, or child. The method includesidentifying an infant, toddler, or child susceptible to necrotizingenterocolitis and administering to the infant, toddler, or child anutritional product including at least 10 wt % of at least one freefatty acid component, fatty acid-containing monoglycerides, orcombinations thereof.

Another embodiment is a method of reducing the incidence of colic in aninfant, toddler, or child. The method includes identifying an infant,toddler, or child susceptible to colic and administering to the infant,toddler, or child a nutritional product including at least 10 wt % of atleast one free fatty acid component, fatty acid-containingmonoglycerides, or combinations thereof.

Another embodiment is a method of reducing the incidence of short bowelsyndrome in an infant, toddler, or child. The method includesidentifying an infant, toddler, or child susceptible to short bowelsyndrome and administering to the infant, toddler, or child anutritional product including at least 10 wt % of at least one freefatty acid component, fatty acid-containing monoglycerides, orcombinations thereof.

It has been discovered that nutritional products such as infant,toddler, and pediatric formulas including predigested fat, such asmonoglycerides and fatty acids as described herein, can reduce theoverall burden on an infant's fat digestive system to improve infant fatdigestion and absorption, including water insoluble/lipid solublenutrient absorption. Specifically, the absorption of predigested fat inthe proximal part of small intestine stimulates CCK secretion, whichpromotes pancreatic alpha cell maturation and the secretion of digestiveenzymes. Also, GLP-1 and GLP-2 secretion is stimulated, which furtherpromotes gut maturation.

Surprisingly, the use of predigested fat and the subsequent secretion ofCCK and GLP-1 retards GI transit and stimulates pancreatic enzymesecretion to allow more complete nutrient digestion and absorption. Thereduction in the amount of nutrients entering the infant's colon resultsin reduced colonic fermentation, which is part of the cause for gas andloose stool problems. In addition, it has been discovered that the useof predigested fat can reduce the incidence of necrotizingenterocolitis, colic, and/or short bowel syndrome.

Further, it has been discovered that the unsaturated fatty acidcomponent of the predigested fat can react with calcium or magnesiumsources and the resultant formed salts are surprisingly bioavailable.Along with providing a good source of calcium or magnesium, thesecalcium or magnesium salts are also surprisingly bland, in contrast withfatty acids which are generally bitter and impart a strong throatburning sensation. Additionally, it has been discovered that the calciumor magnesium fatty acid salts surprisingly act to stabilize nutritionalemulsions, as they do not form a hard to disperse settlement in theemulsion like many insoluble calcium salts are prone to do. As such, inmany embodiments, the inclusion of calcium or magnesium fatty acid saltsas part of the predigested fat may eliminate the need for stabilizers,such as carrageenan.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B show a drawing of a control emulsion and an experimentalemulsion as prepared in Example 19.

FIG. 2 is a chart showing the effect of diet on stool consistency.

DETAILED DESCRIPTION OF THE DISCLOSURE

The nutritional products described herein comprise predigested fat. Inmany embodiments, the products include fatty acid-containingmonoglycerides and a fatty acid component such that the predigested fatsystem includes two components. By reducing the burden on the infant,toddler, or child's digestive system, a number of benefits are realizedwhile providing a stable, bioavailable product. These and other featuresof the nutritional products, as well as some of the many optionalvariations and additions, are described in detail hereafter.

The terms “retort packaging” and “retort sterilizing” are usedinterchangeably herein, and unless otherwise specified, refer to thecommon practice of filling a container, most typically a metal can orother similar package, with a nutritional liquid and then subjecting theliquid-filled package to the necessary heat sterilization step, to forma sterilized, retort packaged, nutritional liquid product.

The term “aseptic packaging” as used herein, unless otherwise specified,refers to the manufacture of a packaged product without reliance uponthe above-described retort packaging step, wherein the nutritionalliquid and package are sterilized separately prior to filling, and thenare combined under sterilized or aseptic processing conditions to form asterilized, aseptically packaged, nutritional liquid product.

The terms “fat” and “oil” as used herein, unless otherwise specified,are used interchangeably to refer to lipid materials derived orprocessed from plants or animals. These terms also include syntheticlipid materials so long as such synthetic materials are suitable fororal administration to humans.

The term “shelf stable” as used herein, unless otherwise specified,refers to a nutritional product that remains commercially stable afterbeing packaged and then stored at 18-24° C. for at least 3 months,including from about 6 months to about 24 months, and also includingfrom about 12 months to about 18 months.

The terms “nutritional formulation” or “nutritional product” or“nutritional composition” as used herein, are used interchangeably and,unless otherwise specified, refer to liquid and solid (includingsemi-liquid and semi-solid) human milk fortifiers, liquid and solidpreterm infant formulas, liquid and solid infant formulas, liquid andsolid follow-on formulas, liquid and solid pediatric formulas, andliquid and solid toddler formulas. The solids may be powders that may bereconstituted to form a nutritional liquid, all of which comprise one ormore of fat, protein and carbohydrate and are suitable for oralconsumption by a human.

The term “nutritional liquid” as used herein, unless otherwisespecified, refers to nutritional products in ready-to-drink liquid form,concentrated form, and nutritional liquids made by reconstituting thenutritional powders described herein prior to use.

The term “nutritional powder” as used herein, unless otherwisespecified, refers to nutritional products in flowable or scoopable formthat can be reconstituted with water or another aqueous liquid prior toconsumption and includes both spraydried and drymixed/dryblendedpowders.

The term “infant” as used herein, unless otherwise specified, refers toa person 12 months or younger. The term “preterm infant” as used herein,refers to an infant born prior to 36 weeks of gestation.

The term “toddler” as used herein, unless otherwise specified, refers toa person greater than one year of age to three years of age.

The term “child” as used herein, unless otherwise specified, refers to aperson greater than three years of age to twelve years of age.

The term “predigested fat” as used herein, unless otherwise specified,refers to fatty acid-containing monoglycerides and/or a fatty acidcomponent.

The term “infant formula” as used herein, unless otherwise specified,refers to liquid and solid nutritional products suitable for consumptionby an infant as a main source of nutrition.

The term “preterm infant formula” as used herein, unless otherwisespecified, refers to liquid and solid nutritional products suitable forconsumption by a preterm infant as a main source of nutrition.

The term “human milk fortifier” as used herein, unless otherwisespecified, refers to liquid and solid nutritional products suitable formixing with breast milk or preterm infant formula or infant formula forconsumption by a preterm or term infant.

The term “fatty acid-containing monoglyceride” as used herein, unlessotherwise specified, refers to a glyceride consisting of one fatty acidchain covalently bonded to a glycerol molecule through an ester linkageat one of the Sn-1 (α), Sn-2 (β), or Sn-3 (α′) position of the glycerolmolecule.

The term “fatty acid component” as used herein, unless otherwisespecified, refers to free fatty acids or fatty acid salts such ascalcium or magnesium fatty acid salts derived from a source having lessthan 20% (by weight) total myristic, palmitic, and stearic acid.

The term “lipid soluble nutrient” as used herein, unless otherwisespecified, refers to water insoluble nutrients, such as oil soluble(lipid soluble) vitamins (e.g., vitamins A, D, E, and K), carotenoids(e.g., lutein, beta-carotene, licopene, etc.), glycolipids(gangliosides), sterols, and phytochemicals.

Numerical ranges as used herein are intended to include every number andsubset of numbers within that range, whether specifically disclosed ornot. Further, these numerical ranges should be construed as providingsupport for a claim directed to any number or subset of numbers in thatrange. For example, a disclosure of from 1 to 10 should be construed assupporting a range of from 2 to 8, from 3 to 7, from 5 to 6, from 1 to9, from 3.6 to 4.6, from 3.5 to 9.9, and so forth.

All references to singular characteristics or limitations of the presentdisclosure shall include the corresponding plural characteristic orlimitation, and vice versa, unless otherwise specified or clearlyimplied to the contrary by the context in which the reference is made.

All combinations of method or process steps as used herein can beperformed in any order, unless otherwise specified or clearly implied tothe contrary by the context in which the referenced combination is made.

The various embodiments of the nutritional products of the presentdisclosure may also be substantially free of any optional or selectedingredient or feature described herein, provided that the remainingnutritional product still contains all of the required ingredients orfeatures as described herein. In this context, and unless otherwisespecified, the term “substantially free” means that the selectednutritional product contains less than a functional amount of theoptional ingredient, typically less than 1%, including less than 0.5%,including less than 0.1%, and also including zero percent, by weight ofsuch optional or selected ingredient.

The nutritional products and methods may comprise, consist of, orconsist essentially of the elements of the products as described herein,as well as any additional or optional element described herein orotherwise useful in nutritional product and method applications.

Product Form

The predigested fat-containing nutritional products and associatedmethods of the present disclosure may be formulated and administered inany known or otherwise suitable oral product form. Any solid,semi-solid, liquid, semi-liquid or powder form, including combinationsor variations thereof, are suitable for use herein, provided that suchforms allow for safe and effective oral delivery to the individual ofthe ingredients as also defined herein.

The nutritional products of the present disclosure include predigestedfat as described herein. The products may optionally include fattyacid-containing monoglycerides or a fatty acid component in combinationwith other fat sources as noted below.

The products may include any product form comprising the ingredientsdescribed herein, and which is safe and effective for oraladministration. The nutritional products may be formulated to includeonly the ingredients described herein, or may be modified with optionalingredients to form a number of different product forms.

The nutritional products of the present disclosure are preferablyformulated as dietary product forms, which are defined herein as thoseembodiments comprising the ingredients of the present disclosure in aproduct form that then contains at least one of fat, protein, andcarbohydrate, and preferably also contains vitamins, minerals, orcombinations thereof. In many embodiments, the product will comprisepredigested fat in combination with protein, carbohydrate, vitamins, andminerals to produce a nutritional product.

The nutritional products may be formulated with sufficient kinds andamounts of nutrients to provide a sole, primary, or supplemental sourceof nutrition, or to provide a specialized nutritional product for use inindividuals afflicted with specific diseases or conditions or with atargeted nutritional benefit.

Specific non-limiting examples of product forms suitable for use withthe predigested fat as disclosed herein include, for example, liquid andpowdered human milk fortifiers, liquid and powdered preterm infantformulas, liquid and powdered infant formulas, liquid and powderedelemental and semi-elemental formulas, liquid and powdered pediatricformulas, and liquid and powdered toddler formulas.

Nutritional Liquids

Nutritional liquids include both concentrated and ready-to-feednutritional liquids. These nutritional liquids are most typicallyformulated as suspensions or emulsions.

Nutritional emulsions suitable for use may be aqueous emulsionscomprising proteins, fats, and carbohydrates. These emulsions aregenerally flowable or drinkable liquids at from about 1° C. to about 25°C. and are typically in the form of oil-in-water, water-in-oil, orcomplex aqueous emulsions, although such emulsions are most typically inthe form of oil-in-water emulsions having a continuous aqueous phase anda discontinuous oil phase.

The nutritional emulsions may be and typically are shelf stable. Thenutritional emulsions typically contain up to about 95% by weight ofwater, including from about 50% to about 95%, also including from about60% to about 90%, and also including from about 70% to about 88%, ofwater by weight of the nutritional emulsions. The nutritional emulsionsmay have a variety of product densities, but most typically have adensity greater than about 1.03 g/ml, including greater than about 1.04g/ml, including greater than about 1.055 g/ml, including from about 1.06g/ml to about 1.12 g/ml, and also including from about 1.085 g/ml toabout 1.10 g/ml.

The nutritional emulsions may have a caloric density tailored to thenutritional needs of the ultimate user, although in most instances theemulsions comprise generally at least 19 kcal/fl oz (660 kcal/liter),more typically from about 20 kcal/fl oz (675-680 kcal/liter) to about 25kcal/fl oz (820 kcal/liter), even more typically from about 20 kcal/floz (675-680 kcal/liter) to about 24 kcal/fl oz (800-810 kcal/liter).Generally, the 22-24 kcal/fl oz (740-810 kcal/liter) formulas are morecommonly used in preterm or low birth weight infants, and the 20-21kcal/fl oz (675-680 to 700 kcal/liter) formulas are more often used interm infants. In some embodiments, the emulsion may have a caloricdensity of from about 100 kcal/liter to about 660 kcal/liter, includingfrom about 150 kcal/liter to about 500 kcal/liter.

The nutritional emulsion may have a pH ranging from about 3.5 to about8, but are most advantageously in a range of from about 4.5 to about7.5, including from about 5.5 to about 7.3, including from about 6.2 toabout 7.2.

Although the serving size for the nutritional emulsion can varydepending upon a number of variables, a typical serving size isgenerally at least about 2 mL, or even at least about 5 mL, or even atleast about 10 mL, or even at least about 25 ml, including ranges fromabout 2 mL to about 300 mL, including from about 4 mL to about 250 mL,and including from about 10 mL to about 240 mL.

As noted above, the nutritional products may also be in the form of asemi-liquid, which includes those forms that are intermediate inproperties, such as flow properties, between liquids and solids.Exemplary semi-liquids include thick shakes and liquid gels.

Nutritional Solids

The nutritional solids may be in any solid form but are typically in theform of flowable or substantially flowable particulate compositions, orat least particulate compositions. Particularly suitable nutritionalsolid product forms include spray dried, agglomerated or dryblendedpowder compositions. The compositions can easily be scooped and measuredwith a spoon or similar other device, wherein the compositions caneasily be reconstituted by the intended user with a suitable aqueousliquid, typically water, to form a nutritional formulation for immediateoral or enteral use. In this context, “immediate” use generally meanswithin about 48 hours, most typically within about 24 hours, preferablyright after reconstitution.

The nutritional powders may be reconstituted with water prior to use toa caloric density tailored to the nutritional needs of the ultimateuser, although in most instances the powders are reconstituted withwater to form compositions comprising at least 19 kcal/fl oz (660kcal/liter), more typically from about 20 kcal/fl oz (675-680kcal/liter) to about 25 kcal/fl oz (820 kcal/liter), even more typicallyfrom about 20 kcal/fl oz (675-680 kcal/liter) to about 24 kcal/fl oz(800-810 kcal/liter). Generally, the 22-24 kcal/fl oz (740-810kcal/liter) formulas are more commonly used in preterm or low birthweight infants, and the 20-21 kcal/fl oz (675-680 to 700 kcal/liter)formulas are more often used in term infants. In some embodiments, thereconstituted powder may have a caloric density of from about 50kcal/liter to about 660 kcal/liter, including from about 100 kcal/literto about 500 kcal/liter.

As noted above, the nutritional products may also be in the form of asemi-solid, which includes those forms that are intermediate inproperties, such as rigidity, between solids and liquids. Somesemi-solid examples include puddings, gelatins, and doughs.

Predigested Fat System

A. Fatty Acid-Containing Monoglycerides

In some embodiments, the nutritional products of the present disclosureinclude fatty acid-containing monoglycerides, also known asmonoacylglycerols, alone or in combination with a fatty acid componentas described below. Monoglycerides are normal metabolites in the bodyformed during the breakdown of triglycerides and diglycerides. As noted,the fatty acid-containing monoglycerides may be included in thenutritional products in combination with a fatty acid component, such asfatty acids and/or fatty acid salts as described below, or may beincluded in the nutritional products in the absence of the fatty acidcomponent.

Suitable fatty acid-containing monoglycerides for use in the nutritionalproducts may include fatty acids having a chain length of from 4 to 22carbon atoms, including fatty acids having a chain length of from 14 to20 carbon atoms, and including palmitic acid (16 carbon atoms).Particularly preferred are monoglycerides wherein at least 70% of thefatty acids in the monoglycerides are at the Sn-1 position, includingmonoglycerol palmitate having at least about 70% of the palmitic acidresidues at the Sn-1 position (also referred to as the alpha position),including at least about 80% at the Sn-1 position, and including fromabout 85% to about 100% in the Sn-1 position. Further, in someembodiments, the monoglycerides included in the nutritional productsdescribed herein may include trace amounts of diglycerides, freeglycerol, and/or free fatty acids. As used herein, the term “traceamounts” means amounts not exceeding 10 wt %, but more commonly lessthan 7.5 wt %.

In one specific embodiment, the monoglycerides (and optionally the fattyacid component as discussed below) in the nutritional product arepartially or totally provided to the product through the use ofhydrolyzed lard or hydrolyzed tallow. Lard, tallow, and other animalbased products, can be added to the nutritional product and hydrolyzedinto monoglycerides and fatty acids by pancreatic lipase. Alternatively,the lard or tallow can be hydrolyzed prior to incorporation into thenutritional product to produce monoglycerides and fatty acids, which canbe introduced into the nutritional product. Lard, tallow, or hydrolyzedlard or tallow, can provide a portion or all of the monoglyceridesand/or fatty acids in the nutritional product.

In another embodiment, the monoglycerides in the nutritional product arepartially or totally derived from oils such as vegetable oils, marineoils, fish oils, algae oil, fungal oils, tree resin, and combinationsthereof. Suitable vegetable oils include, for example, olive oil, canolaoil, corn oil, palm oil, soybean oil, and combinations thereof.

The fatty acid-containing monoglycerides are present in the nutritionalproducts in amounts of at least about 10% by weight of the fat componentincluded in the nutritional product, including at least about 15% byweight of the fat component included in the nutritional product,including at least about 20% by weight of the fat component included inthe nutritional product, including from 12% to 45%, including from 15%to 25%, and including about 10%, including about 15%, including about20%, including about 25%, including about 30%, and further includingabout 35%, or even about 40%, or even about 50%, or even about 60%, oreven about 70%, or even about 80%, or even about 90%, or even about 100%by weight of the fat component included in the nutritional product.

In one specific embodiment when the nutritional product is a nutritionalpowder including a fat component of about 28% (by weight of thenutritional powder), the fatty acid-containing monoglycerides arepresent at a level of about 10% (by weight of the fat component), orabout 2.8 grams of fatty acid-containing monoglycerides per 100 grams ofnutritional powder.

In another specific embodiment when the nutritional product is aready-to-feed nutritional liquid including a fat component of about3.67% (by weight of the ready-to-feed nutritional liquid), the fattyacid-containing monoglycerides are present at a level of about 10% (byweight of the fat component), or about 0.367 grams of fattyacid-containing monoglycerides per 100 grams of ready-to-feednutritional liquid.

In another specific embodiment when the nutritional product is aconcentrated nutritional liquid including a fat component of about 7.34%(by weight of the concentrated nutritional liquid), the fattyacid-containing monoglycerides are present at a level of about 10% (byweight of the fat component), or about 0.734 grams of fattyacid-containing monoglycerides per 100 grams of concentrated nutritionalliquid.

In addition to providing the numerous benefits outlined above, the fattyacid-containing monoglycerides also have been found to have antiviraland/or antibacterial activity in the nutritional products. Specifically,the presence of fatty acid-containing monoglycerides in nutritionalproducts has been found to kill pathogens and/or slow their replication.

B. Fatty Acid Component

In addition to, or in place of, the fatty acid-containing monoglyceridesdescribed above, the nutritional products of the present disclosure mayinclude a fatty acid component comprising fatty acids as a part of thepredigested fat system. Fatty acids are normal metabolites in the bodynotably formed during the breakdown of fat (triglycerides, diglycerides,cholesterol esters, and certain phospholipids). This fatty acidcomponent is separate and distinct from the fatty acid-containingmonoglycerides discussed above.

Any fatty acid beneficial in a nutritional product can be included inthe nutritional products as part of the predigested fat system. In oneembodiment, the fatty acid is an unsaturated free fatty acid. In someembodiments including unsaturated free fatty acids, the total amount ofsaturated free fatty acids with a chain length of longer than 14 carbonatoms is less than 15 wt %. Exemplary fatty acids suitable for inclusionin the nutritional products described herein include, but are notlimited to, arachidonic acid, linolenic acid, docosahexaenoic acid,stearidonic acid, oleic acid, eicosenoic acid, mead acid, erucic acid,nervonic acid, and mixtures and combinations thereof. Particularlypreferred fatty acids include arachidonic acid, linoleic acid, linolenicacid, docosahexaenoic acid, and oleic acid.

The fatty acid component for inclusion in the predigested fat systeminclude those derived from oils such as vegetable oils, marine oils,fish oils, algae oil, fungal oils, animal fats, fractionated animal fatsand combinations thereof. Suitable vegetable oils include, for example,olive oil, canola oil, corn oil, soybean oil, and combinations thereof.In one embodiment, when animal fat is used, the fatty acids are derivedby enzymatic hydrolysis of lard or tallow and the level of palmitic andstearic acid in the resultant fatty acid mixture is reduced to less than20% of the total fatty acids, including less than 2% of the total fattyacids. In another embodiment, at least some of the fatty acids arederived from soybean oil or tree resin. Once derived from the oilsource, the fatty acids are substantially free of monoglycerides,diglycerides and triglycerides.

Generally, the fatty acids will be derived from a source oil thatcontains less than about 20% (by weight) palmitic acid and/or stearicacid and/or myristic acid. In some embodiments the fatty acids will bederived from a source oil that contains less than about 15% (by weight),including less than about 10% (by weight), including less than about 5%(by weight), and including less than 2% (by weight) palmitic acid and/orstearic acid and/or myristic acid.

In one specific embodiment, the fatty acids are derived from a sourceoil that contains less than about 20% (by weight), including from about10% (by weight) to about 15% (by weight) palmitic acid and/or stearicacid and/or myristic acid. In another specific embodiment, thenutritional product includes palmitic acid in an amount of less thanabout 10% (by weight) of the total fatty acids.

In some embodiments, the nutritional products may include the fattyacids in salt form; that is, the fatty acids may be added into thenutritional products as fatty acid salts. In one suitable embodiment,the fatty acids are added to the nutritional product in the form ofcalcium fatty acid salts, magnesium fatty acid salts or a combinationthereof.

The fatty acid salts can be prepared by one skilled in the art based onthe disclosure herein. In one suitable process, emulsions that includeC₁₀-C₂₄ fatty acid calcium salts can be prepared by first preparing thefatty acid salts by using several starting sources of calcium mixed withat least one source of C₁₀-C₂₄ fatty acids. More particularly, in onemethod, a starting source comprising C₁₀-C₂₄ fatty acids in a blend oftriglycerides or free form can be formed by contact with calciumhydroxide and/or calcium carbonate and/or calcium phosphate. In anothermethod, C₁₀-C₂₄ fatty acids in a triglyceride blend or in free form canbe made by contact with hydrated CaCl₂ or Ca(AcO)₂ at a pH of 6 to about7.5.

The above methods can be conducted under an inert atmosphere, e.g.,under N₂ or argon. In other examples, any of the disclosed methods canbe conducted under an ambient atmosphere (e.g., wherein the reaction isnot conducted under a low oxygen atmosphere).

The source comprising the C₁₀-C₂₄ fatty acids and calcium source can bemixed by any methods known in the art. “Mixing” is not meant to imply aparticular outcome of mixing, such as the dissolution of any componentsto a particular level or the formation of a particular composition, suchas homogeneous mixture, although such mixtures can be produced and somecomponents can be dissolved by mixing. Mixing can be vigorous and can beperformed manually or by a mechanical device such as, but not limitedto, a static mixer, a magnetic stirrer, a shaker, spinner, or rotatingdevice. Mixing can be performed by forcing or bubbling a gas through themixture or by sonication.

Mixing the source of C₁₀-C₂₄ fatty acids with a calcium source can beperformed for at least 1 minute. Mixing can also be performed for atleast 1, 5, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85,90, 95, or 100 minutes, where any of the stated values can form an upperor lower endpoint as appropriate.

Mixing can be performed at various temperatures, but, typically, themethod takes place at an elevated temperature. The precise elevatedtemperature may depend on the particular starting sources of C₁₀-C₂₄fatty acids or calcium and amounts thereof being used. Suitabletemperatures at which the disclosed mixing can be performed include, butare not limited to, from about 4 to about 100° C., from about 10 toabout 100° C., from about 15 to about 100° C., or from about 20 to about70° C.

The sources comprising C₁₀-C₂₄ fatty acids or calcium may also be heatedprior to mixing. Such a pre-heating step can be performed at any of thetemperatures or temperature ranges described herein.

In some embodiments, mixing of the C₁₀-C₂₄ fatty acids and calcium canbe conducted under reduced pressure. A suitable pressure is less than orequal to about 1 Torr or less than or equal to about 0.1 Torr.

In one desirable embodiment, the C₁₀-C₂₄ fatty acid calcium salts areprepared by adding free C₁₀-C₂₄ unsaturated fatty acids and a calciumsource, such as Ca(OH)₂, CaCl₂, CaCO₃, Ca-citrate or a mixture of thesesalts, to form an oil blend. More particularly, the fatty acids aredissolved in a warm aqueous solution (e.g., having a temperature of fromabout 40 to about 80° C.). The pH of the solution may be adjusted,typically to a pH of about 10-11, using KOH or NaOH. Calcium is thenadded to the dissolved fatty acid-containing solution. Typically, thefatty acids and calcium are allowed to sit for 10 minutes to ensure acomplete reaction between the fatty acids and the calcium ions. Themixture is then homogenized to form the oil blend.

In another desirable embodiment, a mixture of calcium fatty acid saltsincluding fatty acids from fish oil, algae oil, fungal oil, and soy oilis prepared as part of the predigested fat system. The fish oil, algaeoil, fungal oil and soy oil are mixed together and hydrolyzed bypotassium hydroxide under a nitrogen blanket. A calcium source, such ascalcium chloride, is then added to the mixture to react with the fattyacids to produce insoluble calcium fatty acids salts. The insolublefatty acid salts can be isolated by filtering, and washed with waterprior to vacuum drying.

It has surprisingly been found that although fatty acid salts, such ascalcium fatty acid salts, are generally insoluble in nutritionalproducts, they do not settle in solution to form a layer ofhard-to-redisperse sediment. Thus, the use of calcium and/or magnesiumfatty acid salts allows for better calcium/magnesium delivery and, inmany embodiments, may eliminate the need for additional stabilizers,such as carrageenan, such that the product can be substantially orcompletely “carrageenan free.”

Accordingly, the use of fatty acid salts allows for improved calciumand/or magnesium and fatty acid bioavailability as compared to productsusing calcium phosphate or calcium carbonate at the calcium source.

Moreover, it has been found that the use of the fatty acid salts in thenutritional products of the present disclosure provides bioavailablefatty acids such as arachidonic acid (ARA) and the like, which are shownto enhance the growth of infants. The use of the predigested fat alsoprovides a creamy nutritional product with improved product stabilityand longer shelf life.

The nutritional products generally include fatty acids or fatty acidsalts in an amount of at least about 10% (by weight) of the fatcomponent included in the nutritional product, including at least about15%, including at least about 20%, including from about 10% to about60%, including from about 15% to about 40%, and including from about 15%to about 35%, including about 10%, including about 15%, including about20%, including about 25%, including about 30%, including about 35%, andfurther including about 40%, or even about 50%, or even about 60%, oreven about 70%, or even about 80%, or even about 90%, or even about 100%by weight of the fat component included in the nutritional product.

In some embodiments, the nutritional products include a mixture of afatty acid component and fatty-acid containing monoglycerides. In theseembodiments, the nutritional product contains the mixture in an amountof at least 10% (by weight) of the fat component included in thenutritional product, including at least about 15%, including at leastabout 20%, including from about 10% to about 40%, including from about20% to about 65%, including from about 25% to about 50%, including fromabout 15% to about 30%, and including from about 15% to about 25%,including about 10%, including about 15%, including about 20%, includingabout 25%, including about 30%, including about 35%, and furtherincluding about 40% or even about 50%, or even about 60%, or even about70%, or even about 80%, or even about 90%, or even about 100% by weightof the fat component included in the nutritional product.

In other embodiments, the nutritional products include a fatty acidcomponent, fatty-acid containing monoglycerides, or combinations thereofin an amount of at least 0.2% (by weight), including at least 1% (byweight), including at least 2% (by weight), and including at least 5%(by weight) of total dry matter in the nutritional product.

Macronutrients

Although total concentrations or amounts of the fat, protein, andcarbohydrates may vary depending upon the product type (i.e., human milkfortifier, infant formula, etc.), product form (i.e., nutritional solid,powder, ready-to-feed liquid, or concentrated liquid) and targeteddietary needs of the intended user, such concentrations or amounts mosttypically fall within one of the following embodied ranges, inclusive ofany other fat, protein, and/or carbohydrate ingredients as describedherein.

For the liquid preterm and term infant formula products, carbohydrateconcentrations most typically range from about 5% to about 40%,including from about 7% to about 30%, including from about 10% to about25%, by weight of the preterm or term infant formula; fat concentrations(including both predigested fat and any other fat sources) mosttypically range from about 1% to about 30%, including from about 2% toabout 15%, and also including from about 3% to about 10%, by weight ofthe preterm or term infant formula; and protein concentrations mosttypically range from about 0.5% to about 30%, including from about 1% toabout 15%, and also including from about 2% to about 10%, by weight ofthe preterm or term infant formula.

For the liquid human milk fortifier products carbohydrate,concentrations most typically range from about 10% to about 75%,including from about 10% to about 50%, including from about 20% to about40%, by weight of the human milk fortifier; fat concentrations(including both predigested fat and any other fat sources) mosttypically range from about 10% to about 40%, including from about 15% toabout 37%, and also including from about 18% to about 30%, by weight ofthe human milk fortifier; and protein concentrations most typicallyrange from about 5% to about 40%, including from about 10% to about 30%,and also including from about 15% to about 25%, by weight of the humanmilk fortifier.

The level or amount of carbohydrates, fats, and/or proteins in theliquid nutritional products may also be characterized in addition to orin the alternative as a percentage of total calories in the nutritionalproducts as set forth in the following Table. These macronutrients forliquid nutritional products of the present disclosure are most typicallyformulated within any of the caloric ranges (embodiments A-F) describedin the following Table (each numerical value is preceded by the term“about”).

Nutrient % Total Cal. Embodiment A Embodiment B Embodiment CCarbohydrate 0-98 2-96 10-75 Protein 0-98 2-96  5-70 Fat 0-98 2-96 20-85Embodiment D Embodiment E Embodiment F Carbohydrate 30-50 25-50 25-50 Protein 15-35 10-30 5-30 Fat 35-55  1-20 2-20

In one specific example, liquid infant formulas (both ready-to-feed andconcentrated liquids) include those embodiments in which the proteincomponent may comprise from about 7.5% to about 25% of the caloriccontent of the formula; the carbohydrate component may comprise fromabout 35% to about 50% of the total caloric content of the infantformula; and the fat component may comprise from about 30% to about 60%of the total caloric content of the infant formula. These ranges areprovided as examples only, and are not intended to be limiting.Additional suitable ranges are noted in the following Table (eachnumerical value is preceded by the term “about”).

Nutrient % Total Cal. Embodiment G Embodiment H Embodiment ICarbohydrates: 20-85  30-60 35-55 Fat: 5-70 20-60 25-50 Protein: 2-75 5-50  7-40

When the nutritional product is a powdered preterm or term infantformula, the protein component is present in an amount of from about 5%to about 35%, including from about 8% to about 12%, and including fromabout 10% to about 12% by weight of the preterm or term infant formula;the fat component is present in an amount of from about 10% to about35%, including from about 25% to about 30%, and including from about 26%to about 28% by weight of the preterm or term infant formula; and thecarbohydrate component is present in an amount of from about 30% toabout 85%, including from about 45% to about 60%, and including fromabout 50% to about 55% by weight of the preterm or term infant formula.

For powdered human milk fortifiers the protein component is present inan amount of from about 1% to about 55%, including from about 10% toabout 50%, and including from about 10% to about 30% by weight of thehuman milk fortifier; the fat component is present in an amount of fromabout 1% to about 30%, including from about 1% to about 25%, andincluding from about 1% to about 20% by weight of the human milkfortifier; and the carbohydrate component is present in an amount offrom about 15% to about 75%, including from about 15% to about 60%, andincluding from about 20% to about 50% by weight of the human milkfortifier.

The total amount or concentration of fat, carbohydrate, and protein, inthe powdered nutritional products of the present disclosure can varyconsiderably depending upon the selected product and dietary or medicalneeds of the intended user. Additional suitable examples ofmacronutrient concentrations are set forth below. In this context, thetotal amount or concentration refers to all fat, carbohydrate, andprotein sources in the powdered product. For powdered nutritionalproducts, such total amounts or concentrations are most typically andpreferably formulated within any of the embodied ranges described in thefollowing Table (all numbers have “about” in front of them).

Nutrient % Total Cal. Embodiment J Embodiment K Embodiment LCarbohydrate 1-85 30-60 35-55 Fat 5-70 20-60 25-50 Protein 2-75  5-50 7-40Fat

The nutritional products of the present disclosure may, in addition topredigested fat, comprise an additional source or sources of fat (thetotal amount of fat being referred to herein as the “fat component” or“fat system” of the nutritional product). Suitable additional sources offat for use herein include any fat or fat source that is suitable foruse in an oral nutritional product and is compatible with the elementsand features of such products.

Non-limiting examples of suitable additional fats or sources thereof foruse in the nutritional products described herein include coconut oil,fractionated coconut oil, soybean oil, corn oil, olive oil, saffloweroil, high oleic safflower oil, oleic acids (EMERSOL 6313 OLEIC ACID),MCT oil (medium chain triglycerides), sunflower oil, high oleicsunflower oil, palm and palm kernel oils, palm olein, canola oil, marineoils, fish oils, fungal oils, algae oils, cottonseed oils, andcombinations thereof. In one embodiment, suitable fats or sourcesthereof include oils and oil blends including long chain polyunsaturatedfatty acids (LC-PUFAs), preferably LC-PUFAs having four or more doublebonds. Some non-limiting specific polyunsaturated acids for inclusioninclude, for example, docosahexaenoic acid (DHA), arachidonic acid(ARA), eicosapentaenoic acid (EPA), and the like.

Generally, the predigested fat described herein is included in thenutritional product in combination with one, two, three, four, or moreadditional fat sources. In one embodiment, monoglycerides (desirably inthe form of monoglycerol palmitate), fatty acids (desirably in the formof calcium salts), a high oleic oil, and coconut oil are combinedtogether to provide the fat component in a nutritional product. In thisembodiment, the monoglycerides are present in an amount of from about 1%to about 40%, including from about 10% to about 30%, including about10%, about 15%, about 20%, about 23%, and about 25% by weight of the fatcomponent, the fatty acids are present in an amount of from about 1% toabout 40%, including from about 10% to about 30%, including about 10%,about 15%, about 20%, and about 25% by weight of the fat component, thehigh oleic oil is present in an amount of from about 1% to about 40%,including from about 10% to about 30%, including about 10%, about 15%,about 20%, about 25%, and about 30% by weight of the fat component, andthe coconut oil is present in an amount of from about 1% to about 40%,including from about 10% to about 30%, including about 10%, about 15%,about 17%, about 20%, and about 25% by weight of the fat component.

In another embodiment, fatty acid-containing monoglycerides (desirablyin the form of monoglycerol palmitate), a fatty acid component(desirably in the form of calcium salts), a high oleic safflower oil,and coconut oil are combined together to provide the fat component in anutritional product. In this embodiment, the monoglycerides are presentin an amount of from about 1% to about 40%, including from about 10% toabout 30%, including about 10%, about 15%, about 20%, about 23% andabout 25% by weight of the fat component, the fatty acids are present inan amount of from about 1% to about 40%, including from about 10% toabout 30%, including about 10%, about 15%, about 20%, and about 25% byweight of the fat component, the high oleic oil is present in an amountof from about 1% to about 40%, including from about 10% to about 30%,including about 10%, about 15%, about 20%, about 25%, and about 30% byweight of the fat component, and the coconut oil is present in an amountof from about 1% to about 40%, including from about 10% to about 30%,including about 10%, about 15%, about 17%, about 20%, and about 25% byweight of the fat component.

In another embodiment, fatty acid-containing monoglycerides (desirablyin the form of monoglycerol palmitate), a fatty acid component(desirably in the form of calcium salts), a high oleic safflower oil,coconut oil, DHA-containing oil, and ARA-containing oil are combinedtogether to provide the fat component in a nutritional product. In thisembodiment, the monoglycerides are present in an amount of from about 1%to about 40%, including from about 10% to about 30%, including about10%, about 15%, about 20%, about 23%, and about 25% by weight of the fatcomponent, the fatty acids are present in an amount of from about 1% toabout 40%, including from about 10% to about 30%, including about 10%,about 15%, about 20%, and about 25% by weight of the fat component, thehigh oleic oil is present in an amount of from about 1% to about 40%,including from about 10% to about 30%, including about 10%, about 15%,about 20%, about 25%, and about 30% by weight of the fat component, andthe coconut oil is present in an amount of from about 1% to about 40%,including from about 10% to about 30%, including about 10%, about 15%,about 17%, about 20%, and about 25% by weight of the fat component. TheDHA-containing oil is present in an amount of from about 1% to about10%, including about 5% by weight of the fat component and theARA-containing oil is present in an amount of from about 1% to about10%, including about 5% by weight of the fat component.

In another embodiment, the fat component comprises about 38% (by weight)high oleic safflower oil, about 17% (by weight) coconut oil, about 23%(by weight) monoglycerol palmitate, about 20% (by weight) calcium fattyacid salts, about 0.5% (by weight) DHA-containing oil, and about 1.0%(by weight) ARA-containing oil.

Protein

The nutritional products of the present disclosure may optionallyfurther comprise protein in addition to the predigested fat. Any proteinsource that is suitable for use in oral nutritional products and iscompatible with the elements and features of such products is suitablefor use in combination with the predigested fat.

Non-limiting examples of suitable protein or sources thereof for use inthe nutritional products include hydrolyzed, partially hydrolyzed ornon-hydrolyzed proteins or protein sources, which may be derived fromany known or otherwise suitable source such as milk (e.g., casein,whey), animal (e.g., meat, fish), cereal (e.g., rice, corn), vegetable(e.g., soy) or combinations thereof. Non-limiting examples of suchproteins include milk protein isolates, milk protein concentrates asdescribed herein, casein protein isolates, extensively hydrolyzedcasein, whey protein, sodium or calcium caseinates, whole cow milk,partially or completely defatted milk, soy protein isolates, soy proteinconcentrates, and so forth.

Carbohydrate

The nutritional products of the present disclosure may furtheroptionally comprise any carbohydrates that are suitable for use in anoral nutritional product and are compatible with the elements andfeatures of such products.

Non-limiting examples of suitable carbohydrates or sources thereof foruse in the nutritional products described herein may includemaltodextrin, hydrolyzed or modified starch or cornstarch, glucosepolymers, corn syrup, corn syrup solids, rice-derived carbohydrates,pea-derived carbohydrates, potato-derived carbohydrates, tapioca,sucrose, glucose, fructose, lactose, high fructose corn syrup, honey,sugar alcohols (e.g., maltitol, erythritol, sorbitol), artificialsweeteners (e.g., sucralose, acesulfame potassium, stevia) andcombinations thereof.

Other Optional Ingredients

The nutritional products of the present disclosure may further compriseother optional components that may modify the physical, chemical,aesthetic or processing characteristics of the products or serve aspharmaceutical or additional nutritional components when used in thetargeted population. Many such optional ingredients are known orotherwise suitable for use in medical food or other nutritional productsor pharmaceutical dosage forms and may also be used in the compositionsherein, provided that such optional ingredients are safe for oraladministration and are compatible with the ingredients in the selectedproduct form.

Non-limiting examples of such optional ingredients includepreservatives, anti-oxidants, emulsifying agents, buffers,fructooligosaccharides, galactooligosaccharides, prebiotics,pharmaceutical actives, additional nutrients as described herein,colorants, flavors, thickening agents and stabilizers, emulsifyingagents, lubricants, and so forth.

The nutritional products may further comprise a sweetening agent,preferably including at least one sugar alcohol such as maltitol,erythritol, sorbitol, xylitol, mannitol, isolmalt, and lactitol, andalso preferably including at least one artificial or high potencysweetener such as acesulfame K, aspartame, sucralose, saccharin, stevia,and tagatose. These sweetening agents, especially as a combination of asugar alcohol and an artificial sweetener, are especially useful informulating liquid beverage embodiments of the present disclosure havinga desirable favor profile. These sweetener combinations are especiallyeffective in masking undesirable flavors sometimes associated with theaddition of vegetable proteins to a liquid beverage. Optional sugaralcohol concentrations in the nutritional product may range from atleast 0.01%, including from 0.1% to about 10%, and also including fromabout 1% to about 6%, by weight of the nutritional product. Optionalartificial sweetener concentrations may range from about 0.01%,including from about 0.05% to about 5%, also including from about 0.1%to about 1.0%, by weight of the nutritional product.

A flowing agent or anti-caking agent may be included in the nutritionalproducts as described herein to retard clumping or caking of the powderover time and to make a powder embodiment flow easily from itscontainer. Any known flowing or anti-caking agents that are known orotherwise suitable for use in a nutritional powder or product form aresuitable for use herein, non limiting examples of which includetricalcium phosphate, silicates, and combinations thereof. Theconcentration of the flowing agent or anti-caking agent in thenutritional product varies depending upon the product form, the otherselected ingredients, the desired flow properties, and so forth, butmost typically range from about 0.1% to about 4%, including from about0.5% to about 2%, by weight of the nutritional product.

A stabilizer may also be included in the nutritional products. Anystabilizer that is known or otherwise suitable for use in a nutritionalproduct is also suitable for use herein, some non-limiting examples ofwhich include carrageenan and gums such as xanthan gum. The stabilizermay represent from about 0.1% to about 5.0%, including from about 0.5%to about 3%, including from about 0.7% to about 1.5%, by weight of thenutritional product.

The nutritional products compositions may further comprise any of avariety of other vitamins or related nutrients, non-limiting examples ofwhich include vitamin A, vitamin D, vitamin E, vitamin K, thiamine,riboflavin, pyridoxine, vitamin B₁₂, carotenoids (e.g., beta-carotene,zeaxanthin, lutein, lycopene), niacin, folic acid, pantothenic acid,biotin, vitamin C, choline, inositol, salts and derivatives thereof, andcombinations thereof.

The nutritional products may further comprise any of a variety of otheradditional minerals, non-limiting examples of which include calcium,phosphorus, magnesium, iron, zinc, manganese, copper, sodium, potassium,molybdenum, chromium, chloride, and combinations thereof. Further, insome embodiments, the nutritional products may be free of carrageenan.

Methods of Manufacture

The nutritional products of the present disclosure may be prepared byany known or otherwise effective manufacturing technique for preparingthe selected product solid or liquid form. Many such techniques areknown for any given product form such as nutritional liquids or powdersand can easily be applied by one of ordinary skill in the art to thenutritional products described herein.

The nutritional products of the present disclosure can therefore beprepared by any of a variety of known or otherwise effective product ormanufacturing methods. In one suitable manufacturing process, forexample, at least three separate slurries are prepared, including aprotein-in-fat (PIF) slurry, a carbohydrate-mineral (CHO-MIN) slurry,and a protein-in-water (PIW) slurry. The PIF slurry is formed by heatingand mixing the oil (e.g., monoglyceride and/or fatty acids, fatty acidcontaining oil, canola oil, corn oil, etc.) and then adding anemulsifier (e.g., lecithin), fat soluble vitamins, and a portion of thetotal protein (e.g., milk protein concentrate, etc.) with continued heatand agitation. The CHO-MIN slurry is formed by adding with heatedagitation to water: minerals (e.g., potassium citrate, dipotassiumphosphate, sodium citrate, etc.), trace and ultra trace minerals (TM/UTMpremix), and/or thickening or suspending agents (e.g., avicel, gellan,carrageenan). The resulting CHO-MIN slurry is held for 10 minutes withcontinued heat and agitation before adding additional minerals (e.g.,potassium chloride, magnesium carbonate, potassium iodide, etc.), and/orcarbohydrates (e.g., fructooligosaccharide, sucrose, corn syrup, etc.).The PIW slurry is then formed by mixing with heat and agitation theremaining protein, if any.

In one specific embodiment of the present disclosure, all, or a portionof, the predigested fat included in the nutritional product can be addedto the CHO-MIN slurry, which contains less than 5% (by weight of theCHO-MIN slurry) of fat in the form of triglycerides. In this embodiment,at least 5% (by weight) of the total fat present in the nutritionalproduct is in the form of predigested fat and is added to the CHO-MINslurry. In some embodiments, at least 5% (by weight), including at least10% (by weight), including at least 20% (by weight), including at least30% (by weight), including at least 40% (by weight), including at least50% (by weight), including at least 60% (by weight), including at least70% (by weight), including at least 80% (by weight), including at least90% (by weight), and including 100% (by weight) of the total predigestedfat included in the nutritional product is added to the CHO-MIN slurry.In one particular embodiment, lipid soluble nutrients, such as mixedcarotenoids or vitamins A, D, E, and K, are dissolved in the predigestedfat prior to the predigested fat being added to the CHO-MIN slurry orduring the manufacture of the CHO-MIN slurry. By adding the predigestedfat to the CHO-MIN slurry as opposed to the PIF slurry, the stability ofthe finished nutritional composition can be improved.

The resulting slurries are then blended together with heated agitationand the pH adjusted to 6.6-7.0, after which the composition is subjectedto high-temperature short-time (HTST) processing during which thecomposition is heat treated, emulsified and homogenized, and thenallowed to cool. Water soluble vitamins and ascorbic acid are added, thepH is adjusted to the desired range if necessary, flavors are added, andwater is added to achieve the desired total solid level. The compositionis then aseptically packaged to form an aseptically packaged nutritionalemulsion. This emulsion can also be filled and then sterilized to form aready-to-feed or concentrated liquid, or it can be spray dried, drymixedand and/or agglomerated.

The nutritional solid, such as a spray dried nutritional powder ordrymixed nutritional powder, may be prepared by any collection of knownor otherwise effective techniques suitable for making and formulating anutritional powder.

For example, when the nutritional powder is a spray-dried nutritionalpowder, the spray drying step may likewise include any spray dryingtechnique that is known for or otherwise suitable for use in theproduction of nutritional powders. Many different spray drying methodsand techniques are known for use in the nutrition field, all of whichare suitable for use in the manufacture of the spray dried nutritionalpowders herein.

One method of preparing the spray dried nutritional powder comprisesforming and homogenizing an aqueous slurry or liquid comprisingpredigested fat, and optionally protein, carbohydrate, and other sourcesof fat, and then spray drying the slurry or liquid to produce a spraydried nutritional powder. The method may further comprise the step ofspray drying, dry mixing, or otherwise adding additional nutritionalingredients, including any one or more of the ingredients describedherein, to the spray dried nutritional powder.

Other suitable methods for making nutritional products are described,for example, in U.S. Pat. No. 6,365,218 (Borschel, et al.), U.S. Pat.No. 6,589,576 (Borschel, et al.), U.S. Pat. No. 6,306,908 (Carlson, etal.), and U.S. Patent Application 20030118703 A1 (Nguyen, et al.), whichdescriptions are incorporated herein by reference to the extent thatthey are consistent herewith.

Methods of Use

In accordance with the present disclosure, and as further describedbelow, the nutritional products described herein can be utilized for anumber of purposes including, for example, improving digestion,improving nutrient absorption, improving tolerance, decreasing theincidence of necrotizing enterocolitis, decreasing the incidence ofcolic, and decreasing the incidence of short bowel syndrome. Theindividual (infant, toddler, or child) utilizing the nutritionalproducts described herein may actually have or be afflicted with thedisease or condition described (i.e., may actually have digestion,nutrient absorption and/or tolerance problems or may actually havenecrotizing enterocolitis, colic, or short bowel syndrome), or may besusceptible to, or at risk of, getting the disease or condition (thatis, may not actually yet have the disease or condition, but is atelevated risk as compared to the general population for getting it dueto certain conditions, family history, etc.) Whether the individualactually has the disease or condition, or is at risk or susceptible tothe disease or condition, the individual is classified herein as “inneed of” assistance in dealing with and combating the disease orcondition. For example, an infant may actually have necrotizingenterocolitis or may be at risk of getting necrotizing enterocolitis(susceptible to getting necrotizing enterocolitis) due to prematurebirth. Similarly, in another example, an infant may actually havetolerance and/or digestion and/or nutrient absorption issues, or may beat risk of (susceptible to) getting one or more of these conditions dueto having other diseases or conditions, or a family history of suchproblems. Whether the individual actually has the disease or condition,or is only at risk of or susceptible to getting the disease orcondition, it is within the scope of the present disclosure to assistthe individual with the nutritional products described herein.

Based on the forgoing, because some of the method embodiments of thepresent disclosure are directed to specific subsets or subclasses ofidentified individuals (that is, the subset or subclass of individuals“in need” of assistance in addressing one or more specific diseases orspecific conditions noted herein), not all individuals can benefit fromall method embodiments described herein as not all individuals will fallwithin the subset or subclass of individuals as described herein forcertain diseases or conditions.

The nutritional products as described herein comprise predigested fatdesirably in combination with one or more additional fat sources toprovide a nutritional source for infants, toddlers, and children forimproving digestion and absorption of nutrients. Specifically, similarto the digestion of breast fed infants, as the fat source is at leastpartially digested prior to entering the duodenum, more time is allowedfor the nutrients to be absorbed by the infant, particularly in theintestines, and the amount of nutrients that enter the infant's colon isreduced, thus resulting in less nutrients that can be fermented andproduce gas, which can result in reduced tolerance of a product. Assuch, by utilizing a predigested fat source such as monoglyceridesand/or fatty acids in a nutritional product, such as an infant formula,it is now possible to provide infants with an alternative, orsupplement, to breast milk that more closely mimics the benefitsthereof.

Along with improved absorption of nutrients as described above, it hasbeen found that the use of predigested fat within a nutritional productalso facilitates formation of micelles when administered with one ormore water insoluble hydrophobic compounds, such as oil soluble (lipidsoluble) vitamins (vitamins A, D, E, and K), carotenoids (e.g., lutein,beta-carotene licopene etc.), glycolipids (gangliosides), sterols, andphytochemicals. Formation of these micelles allows the insolublehydrophobic compounds to be dissolved into digesta, which is a step forabsorption by the villi of the intestine. In addition, the predigestedfat will be used to re-synthesize triglycerides to form chylomicron.Chylomicron carries the water insoluble hydrophobic compounds into thelymph, wherein circulation transports the insoluble hydrophobiccompounds to the targeted organs and/or tissues to produce desiredphysiological effects.

In addition to the benefits discussed above, it has been discovered thatnutritional products including predigested fat stimulate cholecystokinin(CCK) production in the duodenum, which stimulates pancreatic lipaseproduction. This production results in further digestion of nutrientsand reduces upper gastrointestinal contractions, which allows more timefor absorption. Thus, the use of predigested fat in the nutritionalproducts reduces the total amount of nutrients that enter the colon,which can be fermented and produce gas and a bloated feeling. As such,the use of predigested fats in nutritional products can improvetolerance by improving nutrient digestion and absorption with less gas.This can be particularly important with infants, as tolerance can be anissue in some infants.

Along with stimulating CCK production, it has been discovered thatpredigested fat also induces secretion of the intestinal growth hormone,Glucagon-like peptide-2 (GLP-2). GLP-2 can enhance the maturation of theinfant's gut, which results in better digestion and nutrient absorption.

It has further been found that the nutritional products as describedherein comprising predigested fat can be used to provide a nutritionalsource for infants, toddlers, or children that may reduce the incidenceof necrotizing enterocolitis (NEC), colic, and/or short bowel syndrome.

In addition, in embodiments where the nutritional product ismanufactured by a process in which at least a portion of the predigestedfat (or in some embodiments all of the predigested fat) is added to thecarbohydrate-mineral slurry as opposed to the protein in fat slurry, theresulting stability of the nutritional product (generally in the form ofa nutritional emulsion) may be improved.

EXAMPLES

The following examples illustrate specific embodiments and/or featuresof the nutritional products of the present disclosure. The examples aregiven solely for the purpose of illustration and are not to be construedas limitations of the present disclosure, as many variations thereof arepossible without departing from the spirit and scope of the disclosure.All exemplified amounts are weight percentages based upon the totalweight of the composition, unless otherwise specified.

The exemplified compositions are shelf stable nutritional productsprepared in accordance with the manufacturing methods described herein,such that each exemplified product, unless otherwise specified, includesan aseptically processed embodiment and a retort packaged embodiment.

The nutritional liquid embodiments are aqueous oil-in-water emulsionsthat are packaged in 240 ml plastic containers and remain physicallystable for 12-18 months after formulation/packaging at storagetemperatures ranging from 1-25° C.

Examples 1-4

Examples 1-4 illustrate lactose-free infant nutritional emulsions of thepresent disclosure, the ingredients of which are listed in the Tablebelow. All ingredient amounts are listed as kilogram per 1000 kilogrambatch of product, unless otherwise specified.

Exam- Exam- Exam- Exam- Ingredient ple 1 ple 2 ple 3 ple 4 Water Q.SQ.S. Q.S. Q.S. Maltodextrin 53 43.3 50 60 Sucrose 16.5 25 19.2 16.38Milk Protein isolate 15.65 15.65 15.65 15.65 Corn Oil 12 12 12 12 HighOleic Safflower Oil 10 10 10 10 Monoglycerol Palmitate 10 9 8 7 C₁₀-C₂₄fatty acid 6.0 7 8 9 calcium salt Coconut oil 2 2 2 2 Fungal oil 0.3 0.30.3 0.3 Lecithin 0.1 0.1 0.1 0.1 Potassium phosphate 0.96 0.96 0.96 0.96dibasic Potassium chloride 0.3 0.3 0.3 0.3 Ascorbic Acid 0.235 0.2350.235 0.235 Carrageenan 0.150 0.150 0.150 0.150 Potassium Hydroxide0.136 0.136 0.136 0.136 TM/UTM Premix 0.1684 0.1684 0.1684 0.1684Vitamin A, D, E Premix 0.0758 0.0758 0.0758 0.0758 Water sol. Vitamin0.0728 0.0728 0.0728 0.0728 premix Potassium Iodide 0.00022 0.000220.00022 0.00022 Chromium Chloride 0.000217 0.000217 0.000217 0.000217

Examples 5-8

Examples 5-8 illustrate lactose-based nutritional emulsions of thepresent disclosure, the ingredients of which are listed in the Tablebelow. All ingredient amounts are listed as kg per 1000 kg batch ofproduct, unless otherwise specified.

Exam- Exam- Exam- Exam- Ingredient ple 5 ple 6 ple 7 ple 8 Water Q.SQ.S. Q.S. Q.S. Lactose 58 66 71 63 Non-fat Dry Milk 25 10 0 16 WheyProtein 6.4 13 18 10.5 Concentrate High Oleic Safflower Oil 14 14 14 14Coconut Oil 6.2 6.2 6.2 6.2 Monoglycerol Palmitate 10 8 6 4 C₁₀-C₂₄Fatty Acids 5.5 7.5 9.5 11.5 Fructooligosaccharides/ 9 9 9 9Galactooligosaccharides Fungal Oil 0.3 0.3 0.3 0.3 Potassium Phosphate0.96 0.96 0.96 0.96 Dibasic Calcium Hydroxide 0.78 1.07 1.36 1.64Potassium Chloride 0.3 0.3 0.3 0.3 Ascorbic Acid 0.235 0.235 0.235 0.235Carrageenan 0.150 0.150 0.150 0.150 Potassium Hydroxide 0.136 0.1360.136 0.136 TM/UTM Premix 0.1684 0.1684 0.1684 0.1684 Vitamin A, D, EPremix 0.0758 0.0758 0.0758 0.0758 Water sol. Vitamin 0.0728 0.07280.0728 0.0728 Premix Potassium Iodide 0.00022 0.00022 0.00022 0.00022Chromium Chloride 0.000217 0.000217 0.000217 0.000217

Examples 9-12

Examples 9-12 illustrate soy-based infant nutritional emulsions of thepresent disclosure, the ingredients of which are listed in the Tablebelow. All ingredient amounts are listed as kilogram per 1000 kilogrambatch of product, unless otherwise specified.

Exam- Exam- Exam- Exam- Ingredient ple 9 ple 10 ple 11 ple 12 Water Q.SQ.S. Q.S. Q.S. Corn Syrup Solids 53 43.3 50 60 Sucrose 16.5 25 19.216.38 Soy Protein Isolate 19.5 19.5 19.5 19.5 Corn Oil 12 12 12 12 HighOleic Safflower Oil 10 10 10 10 Monoglycerol Palmitate 10 9 8 7 C₁₀-C₂₄Fatty Acids 6.0 7 8.0 9 Fungal Oil 0.3 0.3 0.3 0.3 L-cystine 2.3 2.3 2.32.3 L-tyrosine 1.1 1.1 1.1 1.1 Calcium Hydroxide 0.09 1.0 1.1 1.2L-tryptophan 0.66 0.66 0.66 0.66 Potassium Phosphate 0.96 0.96 0.96 0.96Dibasic Potassium Chloride 0.3 0.3 0.3 0.3 Ascorbic Acid 0.235 0.2350.235 0.235 Carrageenan 0.150 0.150 0.0 0.0 Potassium Hydroxide 0.1360.136 0.136 0.136 TM/UTM Premix 0.1684 0.1684 0.1684 0.1684 Vitamin A,D, E Premix 0.0758 0.0758 0.0758 0.0758 Water Sol. Vitamin 0.0728 0.07280.0728 0.0728 Premix Potassium Iodide 0.00022 0.00022 0.00022 0.00022

Examples 13-16

Examples 13-16 illustrate hydrolyzed protein based infant nutritionalemulsions of the present disclosure, the ingredients of which are listedin the Table below. All ingredient amounts are listed as kilogram per1000 kilogram batch of product, unless otherwise specified.

Exam- Exam- Exam- Exam- Ingredient ple 13 ple 14 ple 15 ple 16 WaterQ.S. Q.S. Q.S. Q.S. Sucrose 42 42 42 42 Starch 21.8 21.8 21.8 21.8Hydrolyzed Protein 22.2 22.2 22.2 22.2 High Oleic Safflower Oil 13.713.7 13.7 13.7 MCT Oil 6 6 6 6 Monoglycerol Palmitate 10 9 8 7 C₁₀-C₂₄Fatty Acids 11 9.5 8 6.5 Coconut Oil 5 7.5 9 11.5 Fungal Oil 0.3 0.3 0.30.3 Calcium Hydroxide 1.6 1.29 1.1 0.93 L-Methionine 0.3 0.3 0.3 0.3Potassium Phosphate 0.96 0.96 0.96 0.96 Dibasic Potassium Chloride 0.30.3 0.3 0.3 Ascorbic Acid 0.235 0.235 0.235 0.235 Carrageenan 0.0 0.00.150 0.150 Potassium Hydroxide 0.136 0.136 0.136 0.136 TM/UTM Premix0.1684 0.1684 0.1684 0.1684 Vitamin A, D, E Premix 0.0758 0.0758 0.07580.0758 Water Sol. Vitamin 0.0728 0.0728 0.0728 0.0728 Premix PotassiumIodide 0.00022 0.00022 0.00022 0.00022

Example 17

In this Example, the absorption and the related bioavailability ofC₁₀-C₂₄ fatty acid calcium salts by rats is evaluated.

Thirty rats are randomly assigned to one of three diets (Diet 1, Diet 2,and Diet 3) containing varying proteins and fats. Diets 1-3 are the sameas used in AOAC method 906.48, with the exception that Diets 1-3 have ahigher fat level and include maltodextrin as the carbohydrate source.Diet 1 contains 10 wt % protein available as acid casein and 23.6 wt %fat available as an oil blend containing 30 wt % coconut oil, 30 wt %soybean oil, and 40 wt % high oleic safflower oil (HOSO). Thenutritional profile of Diets 2 and 3 are identical to the nutritionalprofile of Diet 1 except that the protein, fat, carbohydrates andminerals are mixed, homogenized and spray dried. Diet 3 differs fromDiet 2 only in that the HOSO oil is replaced by calcium high oleicsafflower oil fatty acid salts and the tricalcium phosphate is replacedwith potassium phosphate such that the overall nutritional and mineralprofiles of Diet 2 and Diet 3 are the same. The Ca-HOSO fatty acid saltsprovide 100% of the dietary calcium.

The rats are fed one of Diet 1, Diet 2, or Diet 3 for a period of 4weeks. The feed/protein intake and weight gain at the end of the feedingtrial are used to calculate feed conversion (gram of weight gain/gram offeed intake) and protein efficiency ratio (gram of weight gain/gram ofprotein ingested) (PER). If the caloric value (i.e., calories/gram ofsubstance) of the calcium HOSO fatty acid salt is significantly lowerthan that of HOSO due to poor absorption, then it would be expected thatthe rats on Diet 3 will either gain less weight or consume more feed tomaintain their growth, both of which result in a lower feed conversionand PER.

The results shown in the table below indicate that the rats on Diet 3have the same feed conversion or PER as the control, indicating that thecaloric value of the calcium HOSO fatty acid salt is not different fromthe HOSO oil. As such, it is shown that the calcium HOSO fatty acidsalts are highly bioavailable.

Protein Efficiency Ratio Feed Conversion Diet 1 (Control 1)  2.83 +/−0.28* 0.29 +/− 0.03 Diet 2 (Control 2) 3.16 +/− 0.17 0.31 +/− 0.02 Diet3 (fatty acid calcium salt) 3.32 +/− 0.27 0.37 +/− 0.03 *Standarddeviation (n = 10)

Example 18

In this Example, the absorption of soy fatty acid salts by 10 day oldpigs is analyzed.

Sixteen suckling pigs are randomized into two groups and areindividually housed in metabolic cages and trained to take nutritionalemulsions from a bowl within 30 minutes. After one week of training on acommercial ready-to-feed hydrolyzed protein based-formula, the pigs arefed either a commercial hydrolyzed protein-based formula powder(Control) including tricalcium phosphate and calcium carbonate as thecalcium source, or an emulsion (Experimental Emulsion) including calciumsoy fatty acid salts as the calcium source. The protein source andlevel, fat level and mineral profiles are identical for the Control andExperimental Emulsion. The Experimental Emulsion, however, includes soyfatty acids in place of soybean oil in the Control and includes calciumhydroxide as part of the calcium mineral system to neutralize the soyfatty acids. The potassium phosphate level of the Experimental Emulsionis adjusted to match the phosphorus content of the Control. The calciumsoy fatty acids provide 100% of the calcium in the ExperimentalEmulsion.

Apparent fat and calcium digestibility are calculated based on thefollowing formulas after two weeks of feeding:Apparent fat digestibility=((fat intake−fecal fat)/fat intake)*100Apparent calcium digestibility=((calcium intake−fecal calcium)/calciumintake)*100Dry matter digestibility=((dry matter intake−fecal dry matter)/drymatter intake)*100

A decreased feed conversion (weight/feed intake) and decreased fat,calcium, and dry matter digestibility of the Experimental Emulsion wouldindicate that the calcium soy fatty acid salts of the ExperimentalEmulsion are poorly absorbed, and thus, that the caloric value andbioavailability of the calcium are lower for the Experimental Emulsionas compared to the Control.

As shown in the table below, the feed conversion, fat digestibility anddry matter digestibility of the Experimental Emulsion did not differsignificantly from the Control indicating that the calcium soy fattyacid salts of the Experimental Emulsion are highly absorbed andbioavailable for neonatal pigs. Further, the apparent calciumdigestibility data shown below indicate that the calcium soy fatty acidsalts of the Experimental Emulsion are more bioavailable than thecalcium included in the Control (i.e., tricalcium phosphate and calciumcarbonate).

Feed Conversion Apparent Apparent Apparent fat (Gram of weight calciumdry matter digest- gain/gram of digest- digest- ibility feed (drymatter)) ibility ibility Control 97.6 +/− 1.0 0.82 +/− 0.14* 81.8 +/−7.2 97.8 +/− 0.7 Experi- 97.6 +/− 1.4 0.80 +/− 0.15  91.3 +/− 3.3 98.0+/− 1.0 mental Emulsion *Standard deviation (n = 10)

Example 19

In this Example, the emulsifying properties of calcium fatty acid saltsare analyzed.

A first emulsion (Control Emulsion) is prepared by shearing 18 g of 130°F. soy oil containing monoglycerol palmitate (5% of oil by weight) and430 mg of Ca (as tricalcium phosphate) with 500 ml of water using atable top high shear mixer. A second emulsion (Calcium Fatty AcidEmulsion) containing an identical level of calcium and fat (12 g of soyoil plus 6 g of soy fatty acids) as the Control Emulsion is prepared by:(1) dispersing soy fatty acid in oil in water at a temperature of about130° F.; (2) adding 430 mg of Ca as calcium chlorides; (3) adjusting thesolution pH to about 7.0 using KOH; and (4) shearing the mixture using atable top high shear mixture.

Both the Control Emulsion and the Calcium Fatty Acid Emulsion areallowed to sit for a period of three weeks to analyze emulsionseparation. After a single overnight period, the Control Emulsionexhibits a visible phase separation including a creamy layer at the topof the emulsion. (See FIG. 1A). In contrast, after three weeks ofstorage the Calcium Fatty Acid Emulsion exhibits only a slightlydetectable, but not very visible, calcium soap layer on top of theemulsion with the emulsion remaining in one phase. There is no visiblecalcium sediment at the bottom of the Calcium Fatty Acid Emulsion (SeeFIG. 1B).

These results indicate that the calcium fatty acid salts are effectiveemulsifiers and are capable of providing a calcium source to anutritional emulsion that will not substantially settle out of solution.This allows for an emulsion product with improved stability and longershelf life.

Example 20

In this Example, the amount of fat absorption and amount of calciumabsorption from two separate test formulations and a control formulationin 10 day old pigs is measured.

The first test formulation (Formulation 1) includes palm olein oil inthe fat system, the second test formulation (Formulation 2) includespredigested fat in the fat system, and the control formulation(Formulation 3) includes low palmitic acid oil in the fat system. Thecomponents of the fat systems of the three formulations are listed inthe Table below.

Formulation 3 (Control Formulation 1 Formulation 2 Formulation Nutrient(Palm Olein (Predigested Fat including low (grams) Oil Formulation)Formulation) palmitic acid oil) Coconut Oil 37.2 0 84.1 High Oleic 62.8108 111.9 Safflower Oil Soy Fatty 0 56.9 0 Acids ARA oil 3.03 3.03 3.03DHA oil 1.52 1.52 1.52 Monoglycerol 0 65.4 0 Palmitate Lecithin 1.121.12 1.12 Palm Olein 122.7 0 0 Soy Oil 57.1 0 83.8

The three formulations are prepared having nearly identical nutrient andmineral profiles. The fatty acid profile of Formulations 1 and 2 mimicthe breast milk fatty acid profile. Calcium hydroxide is included inFormulation 2 (in an amount sufficient to chelate all of the free fattyacids) as a source of calcium, which reacts with the soy fatty acids toform insoluble calcium fatty acid salts. This reaction eliminates thebitterness and throat burning sensation imparted by free fatty acids. Inaddition, the level of potassium phosphate in Formulation 2 is raised tomatch the phosphorous level of Formulations 1 and 3. The calcium saltused in Formulations 1 and 3 is calcium phoshphate.

Sixty 10 day old pigs (plus or minus two days) are randomized to receiveeither Formulation 1, Formulation 2, or Formulation 3. Pigs areindividually housed in metabolic cages and are fed five times a day forthree weeks after four days of training and adaptation. Fecal materialsfrom day two to day eighteen are collected and analyzed for calciumabsorption and fat absorption. Calcium absorption is calculated as theamount of calcium in the fecal material divided by the amount of calciumin the diet, multiplied by 100. Fat absorption is calculated as theamount of fat in the fecal material divided by the amount of fat in thediet, multiplied by 100. The results are shown in the Table below.

Fat Calcium Absorption Absorption (%) (%) Formulation 1 (palm olein)92.3 ± 3.9 88.9 ± 4.7 Formulation 2 (predigested fat) 98.2 ± 0.7 93.1 ±2.4 Formulation 3 (control: low 98.0 ± 1.4 90.7 ± 3.5 palmitic acid fatsystem)

As the results in the above Table indicate, the use of a predigested fatsystem allows an infant formula to mimic the breast milk fatty acidprofile without the adverse effects on calcium and fat absorption as isexperienced with a palm olein oil fat system. The fat and calciumabsorption rates of Formula 2 (the predigested fat formulation) are atleast as good as those of low palmitic acid formula. These findingsillustrate that calcium soy fatty acid salts are highly bioavailable inneonatal pigs.

Example 21

In this Example, the postprandial increase in CCK production (AUC) andmotilin production (AUC) are evaluated for the pigs of Example 20.

At the conclusion of the fat and calcium absorption analysis describedin Example 20, the pigs being administered Formulation 2 (predigestedfat formulation) or Formulation 3 (control formulation including lowpalmitic acid) are fasted for 12 hours, and fasted blood is drawn toisolate plasma. The pigs are allowed two hours to recover and are thengiven 250 mL of either Formulation 2 or Formulation 3. Postprandialblood samples are drawn at 30 and 60 minutes after feeding and testedfor CCK and motilin. The postprandial increase in CCK (area under curve)and motilin (AUC) is calculated. The results are shown in the tablebelow.

Formulation 3 Formulation 2 (Control: low (predigested fat palmitic acidformulation) formulation) (pg/mL*min) (pg/mL*min) Postprandial increase1935 ± 1464 1046 ± 754 in CCK secretion (area under curve) Motilin AUC483 ± 253  839 ± 403 (post-prandial increase)

The data in the table above show that replacing triglycerides withpredigested fat (monoglycerol palmitate plus soy fatty acids) stimulatespostprandial CCK secretion, which has been shown to stimulate pancreaticdigestive enzyme secretion, enhance gallbladder contraction, and retardmouth to cecum transit. As such, formulations with predigested fat maystimulate more digestible enzyme secretion and slow GI transit to allowmore nutrient digestion and absorption. Thus, formulations includingpredigested fat may improve formula tolerance because undigestednutrients can cause excessive colonic fermentation to cause gas,diarrhea, and stomach distension.

In addition, the data in the table above show that replacingtriglycerides with predigested fat (monoglycerol palmitate plus soyfatty acids) reduces postprandial motilin secretion. It has been shownthat infants with colic have a lower postprandial CCK level but a higherpostprandial moltilin level. This imbalance between the postprandial guthormones causes GI contractions in an infant, which results in abdominalpain. The data in the table above show that the inclusion of predigestedfat enhances the postprandial CCK level of an infant but reduces themoltilin level, thus reducing the hormone imbalance to relieve GIcontractions, abdominal pain, and colic.

Example 22

In this Example, the pigs of Example 20 are used to study the effect ofvarious fat systems on chylomicron triglyceride palmitic acid and Sn-2palmitic acid levels.

The 1 hour postprandial blood sample from each pig is drawn and theplasma isolated, frozen by liquid nitrogen, and stored in a freezer at−80° C. Total plasma lipids are extracted using Folch solvent. Thetriglycerides are isolated by thin layer chromatography. The table belowshows the plasma triglyceride palmitic acid and Sn-2 palmitic acid ofFormulation 1 (palm olein formulation) and Formulation 2 (predigestedfat formulation). The chylomicron triglyceride and Sn-2 palmitic acid ofthe pigs fed these two formulations are also shown in the table.

Plasma Plasma Plasma triglyceride of Formulation 2: triglyceride oftriglyceride of Formulation 1: pigs fed (Predigested pigs fed breastmilk fed (Palm Olein) Formulation 1 Fat) Formulation 2 human infantTriglyceride Sn-2 Triglyceride Sn-2 Triglyceride Sn-2 Triglyceride Sn-2Triglyceride Sn-2 Palmitic 23.3 5.8 18.3 10.6 21.4 5.2 18.5 14.4 25 25.5acid level (%)

As shown in the table above, plasma triglyceride from predigested fatformula fed pigs have a significantly higher plasma triglyceride Sn-2palmitic acid content than the palm olein formula fed pigs. The plasmatriglyceride palmitic acid/Sn-2 palmitic acid ratios are about 1.7 and1.3, respectively, for Formulation 1 and Formulation 2, and it is knownthat this ratio is about 1.1 for breast fed infants. As such, this dataindicates that the predigested fat formulation better mimics breastmilkthan does the palm olein fat formulation.

Example 23

In this Example, the pigs of Example 20 are used to study the effect ofvarious fat systems on blood lutein levels.

Plasma from the 1 hour postprandial blood sample from each pig isextracted using a solvent of chloroform and methanol in a 2:1 ratio. Thesolvent is removed and the resultant lipids are pooled and analyzed forlutein using conventional methods. The table below shows the luteinlevel of the pigs fed Formulation 1 (palm olein formulation),Formulation 2 (predigested fat formulation), and Formulation 3 (lowpalmitic acid formulation) in μg of lutein per mg of lipids.

Formulation 1: Formulation 2: Formulation 3: (Palm Olein) (PredigestedFat) (Low Palmitic Acid) Lutein level N/A* 0.765 μg 0.539 μg *The luteinlevel of Formulation 1 is too low to measure.

As shown in the table above, pigs fed formulations including predigestedfat have an increased absorption of lutein compared to pigs fedformulations including palm olein or low palmitic acid.

Example 24

In this Example, Formulation 2 (predigested fat formulation) andFormulation 3 (low palmitic acid formulation) of Example 20 are used tostudy the effects of various fat systems on micelle lutein levels.

Formulation 2 and Formulation 3 are reconstituted with water (133 g ofpowdered formulation per 1.0 L water), and HCl is added to adjust the pHof the reconstituted formulations to 4.5. The reconstituted formulationsare digested for 1 hour at room temperature by adding 1.00 ml of USPpepsin (56 mg/ml) to 40 ml of the reconstituted formulation. The pH ofthe reconstituted formulations is adjusted to 7.0 after pepsin digestionand then a mixture of 28 mg of USP pancreatin amylast/protease, 28 mg ofUSP pancreatin lipase, and 108 mg of bile extract is added to the pepsindigested formulations. The formulations are further digested at roomtemperature for 2 hours and centrifuged (31,000 g at 20° C. for 3hours). The digested formulations form an oil/cream plug, an aqueousphase, and a sediment layer. The aqueous phase is withdrawn for luteinanalysis of micelles, which act as carriers during the absorption oflutein in the aqueous lumen. The table below shows the level of micellelutein per kg of digested formulation.

Digested Formulation 2: Digested Formulation 3: (Predigested Fat) (LowPalmitic Acid) Micelle Lutein (μg) 0.598 μg 0.246 μg

As shown in the table above, the amount of micelle lutein found in thedigested formulation including predigested fat was more than twice theamount of micelle lutein found in the digested formulation including lowpalmitic acid, thus indicating that the use of predigested fat canincrease lutein absorption.

Example 25

In this Example, the ability of predigested fat to reduce the incidenceof loose stool is analyzed.

Thirty weaned rats are fed a hydrolyzed protein based powder infantformula, comprising MCT oil as 30 wt % of the fat source for anadaptation period of four days. At the end of the adaptation period, therats are randomly assigned to two groups and fed either a ControlFormulation (low palmitic acid powder infant formula) or a TestFormulation (predigested fat containing infant formula). The nutrientprofile of the Control Formulation and the Test Formulation areidentical. The rats are allowed free access to feed and water for aperiod of five days, and the amount of feed ingested and body weight arerecorded daily.

Although there is no significant difference in feed intake or weightgain between the two groups, there is a significant difference in stoolconsistency. The stool consistency of the rats is scored using a 0-5point system during the last two days of feeding. Scoring is based onthe severity and the consistency of the stool sticking to a blottingsheet at the bottom of the cage. A score of 0 indicates normal stool anda score of 5 indicates watery diarrhea. As shown in FIG. 2, the rats fedthe Control Formulation (containing the MCT oil) produced looser stoolsthan the rats fed the Test Formulation (containing the predigested fat).

Example 26

In this Example, the ability of predigested fat to reduce the incidenceof necrotizing enterocolitis (NEC) is analyzed.

Pre-term pigs (92% gestation) delivered via cesarean section areimmediately transferred to an oxygenated incubator (37° C.), and avascular catheter is placed in an umbilical artery. The pigs are giventhree injections (4, 6, and 7 mL/kg body weight) of maternal plasma viathe vascular catheter during the first 24 hours. Total paternalnutrition (TPN) is provided at a rate of 4-6 mL/kg/hour for 24 hours.The pigs are then randomized to receive either a Control Formulation ora PDF Formulation at a rate of 5 mL/kg/hour via an orogastric tube. TheControl Formulation and the PDF Formulation are identical with theexception of the fat systems therein. Specifically, the fat system inthe Control Formulation includes vegetable oil, and the fat system inthe PDF Formulation includes 30 wt % monoglycerol palmitate, 20 wt % soyfatty acids, 26 wt % high oleic safflower oil, 14 wt % coconut oil, and10 wt % tributyrin. Both the Control Formulation and the PDF Formulationinclude 100 g protein, 47 g fat, and 50 g corn syrup per liter offormulation. The pigs are euthanized after 36 hours of enteral feedingand necropsy is conducted to assess the severity of the NEC lesionsusing a scoring system of 1-5 with a score of 1 indicating no signs ofNEC. The results are shown in the table below.

Block 1 Block 2 Control PDF Control PDF Formulation FormulationFormulation Formulation (n = 5) (n = 3) (n = 5) (n = 3) Early NEC 2 0 31 death NEC detected 2 1 0 0 at necropsy Total NEC 4 1 3 1

As shown in the table above, five of the ten pigs (50%) being fed theControl Formulation die of NEC before the conclusion of the enteralfeeding period, but only one of the six pigs (16.7%) fed the PDFFormulation die of NEC before the conclusion of the enteral feedingperiod. In addition, seven of the ten pigs (70%) being fed the ControlFormulation were determined to have NEC at the conclusion of the enteralfeeding period, while only two of the six pigs (33%) being fed the PDFFormulation were determined to have NEC at the conclusion of the enteralfeeding period. Thus, it can be concluded that by replacing a fat systemof vegetable oil with a fat system including predigested fat, theincidence of NEC can be decreased.

What is claimed is:
 1. A method of improving tolerance related tofeeding in an infant, toddler, or child, the method comprisingadministering to the infant, toddler or child a nutritional productcomprising a fat system having at least 10 wt %, by weight of the fatsystem, of at least one of a fatty acid component, fatty acid-containingmonoglycerides having at least 70% of the fatty acids at the Sn-1position, and combinations thereof, wherein the fatty acid componentincludes at least one of free fatty acids, fatty acid salts, andcombinations thereof.
 2. The method of claim 1, wherein the fattyacid-containing monoglycerides are monoglycerol palmitate.
 3. The methodof claim 1, wherein the fatty acid component is in a form selected fromthe group consisting of calcium fatty acid salts, magnesium fatty acidsalts, and combinations thereof.
 4. The method of claim 1, wherein thefatty acid component comprises less than 15 wt % saturated fatty acidswith a chain length of longer than 14 carbon atoms.
 5. The method ofclaim 1, wherein the fatty acid component is derived from a vegetableoil.
 6. The method of claim 5, wherein the vegetable oil comprises atleast one of olive oil, canola oil, corn oil, soybean oil, high oleicsafflower oil, and combinations thereof.
 7. The method of claim 6,wherein the vegetable oil is soybean oil.
 8. The method of claim 1,wherein the fatty acid component is obtained from a source of oil or fatthat contains a total of less than 20 wt % of palmitic acid, stearicacid, myristic acid, or combinations thereof.
 9. The method of claim 8,wherein the fatty acid component is obtained from a source of oil or fatthat contains a total of less than 10 wt % of palmitic acid, stearicacid, myristic acid, or combinations thereof.
 10. The method of claim 1,wherein the fatty acid-containing monoglycerides are obtained byenzymatic hydrolysis of lard, tallow, or combinations thereof.
 11. Themethod of claim 1, wherein from 85% to 100% of the fatty acids in thefatty acid-containing monoglycerides are at the Sn-1 position.
 12. Themethod of claim 11, wherein the fatty acid-containing monoglycerides aremonoglycerol palmitate.
 13. A method of improving tolerance related tofeeding in an infant, the method comprising administering to the infantan infant formula comprising a fat system having at least 10 wt %, byweight of the fat system, of at least one of a fatty acid component,fatty acid-containing monoglycerides having at least 70% of the fattyacids at the Sn-1 position, and combinations thereof, wherein the fattyacid component includes at least one of free fatty acids, fatty acidsalts, and combinations thereof.
 14. The method of claim 13, wherein thefatty acid-containing monoglycerides are monoglycerol palmitate.
 15. Themethod of claim 13, wherein the fatty acid component is in a formselected from the group consisting of calcium fatty acid salts,magnesium fatty acid salts, and combinations thereof.
 16. The method ofclaim 13, wherein the fatty acid component is derived from a vegetableoil.
 17. The method of claim 16, wherein the vegetable oil comprises atleast one of olive oil, canola oil, corn oil, soybean oil, high oleicsafflower oil, and combinations thereof.
 18. The method of claim 13,wherein the fatty acid component is obtained from a source of oil or fatthat contains a total of less than 20 wt % of palmitic acid, stearicacid, myristic acid, or combinations thereof.
 19. The method of claim13, wherein from 85% to 100% of the fatty acids in the fattyacid-containing monoglycerides are at the Sn-1 position.
 20. The methodof claim 19, wherein the fatty acid-containing monoglycerides aremonoglycerol palmitate.